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91.
    
Thirty‐nine tumor‐bearing patients with metastatic melanoma were treated with 3 subcutaneous injections of the MAGE‐3.A1 peptide at monthly intervals. No significant toxicity was observed. Of the 25 patients who received the complete treatment, 7 displayed significant tumor regressions. All but one of these regressions involved cutaneous metastases. Three regressions were complete and 2 of these led to a disease‐free state, which persisted for more than 2 years after the beginning of treatment. No evidence for a cytolytic T lymphocyte (CTL) response was found in the blood of the 4 patients who were analyzed, including 2 who displayed complete tumor regression. Our results suggest that injection of the MAGE‐3.A1 peptide induced tumor regression in a significant number of the patients, even though no massive CTL response was produced. Int. J. Cancer 80:219–230, 1999. © 1999 Wiley‐Liss, Inc.  相似文献   
92.
    
GTP cyclohydrolase (GCH1) is the key‐enzyme to produce the essential enzyme cofactor, tetrahydrobiopterin. The byproduct, neopterin is increased in advanced human cancer and used as cancer‐biomarker, suggesting that pathologically increased GCH1 activity may promote tumor growth. We found that inhibition or silencing of GCH1 reduced tumor cell proliferation and survival and the tube formation of human umbilical vein endothelial cells, which upon hypoxia increased GCH1 and endothelial NOS expression, the latter prevented by inhibition of GCH1. In nude mice xenografted with HT29‐Luc colon cancer cells GCH1 inhibition reduced tumor growth and angiogenesis, determined by in vivo luciferase and near‐infrared imaging of newly formed blood vessels. The treatment with the GCH1 inhibitor shifted the phenotype of tumor associated macrophages from the proangiogenic M2 towards M1, accompanied with a shift of plasma chemokine profiles towards tumor‐attacking chemokines including CXCL10 and RANTES. GCH1 expression was increased in mouse AOM/DSS‐induced colon tumors and in high grade human colon and skin cancer and oppositely, the growth of GCH1‐deficient HT29‐Luc tumor cells in mice was strongly reduced. The data suggest that GCH1 inhibition reduces tumor growth by (i) direct killing of tumor cells, (ii) by inhibiting angiogenesis, and (iii) by enhancing the antitumoral immune response.  相似文献   
93.
    
Children's understanding of linear‐order (e.g., Dan is taller than Lisa, Lisa is taller than Jess) and set‐inclusion (i.e., All tulips are flowers, All flowers are plants) relationships is critical for the acquisition of deductive reasoning, that is, the ability to reach logically valid conclusions from given premises. Behavioral and neuroimaging studies in adults suggest processing differences between these relations: While arguments that involve linear‐orders may be preferentially associated with spatial processing, arguments that involve set‐inclusions may be preferentially associated with verbal processing. In this study, we used functional magnetic resonance imaging to investigate whether these processing differences appear during the period of elementary school in development. Consistent with previous studies in adults, we found that arguments that involve linear‐order and set‐inclusion relationships preferentially involve spatial and verbal brain mechanisms (respectively) in school‐age children (9–14 year olds). Because this neural sensitivity was not related to age, it likely emerges before the period of elementary education. However, the period of elementary education might play an important role in shaping the neural processing of logical reasoning, as indicated by developmental changes in frontal and parietal regions that were dependent on the type of relation. Hum Brain Mapp 36:996–1009, 2015. © 2014 Wiley Periodicals, Inc.  相似文献   
94.
PURPOSE: To prospectively compare the protective effect of acetylcysteine, theophylline, and both agents combined in patients who are admitted to the intensive care unit with at least one risk factor for contrast material-induced nephropathy and who receive at least 100 mL of iodinated contrast medium. MATERIALS AND METHODS: Institutional ethics review board approval and informed consent were obtained. A total of 91 patients (mean age, 58.5 years+/-14.8 [standard deviation]; 31 women, 60 men; 150 examinations) were admitted to the intensive care unit with at least one risk factor for contrast-induced nephropathy and received either (a) 200 mg theophylline 30 minutes before contrast medium administration (group T), (b) 600 mg acetylcysteine twice daily on the day of and (if possible) the day before the examination (group A), or (c) both agents combined (group AT). The primary endpoint for this study was the incidence of contrast-induced nephropathy (chi2 test). RESULTS: Groups T, A, and AT were comparable with regard to baseline creatinine levels and the amount of contrast medium administered. The incidence of contrast-induced nephropathy in groups T, A, and AT was 2%, 12%, and 4%, respectively, and was significantly lower in group T than in group A (P=.047). There was no significant difference in the incidence of contrast-induced nephropathy between groups A and AT (P=.148) or between groups T and AT (P=.53). For group A, serum creatinine did not change after 12, 24, or 48 hours compared with baseline. Creatinine levels in group T decreased 12 hours (1.19 mg/dL+/-0.58; P=.008) and 48 hours (1.16 mg/dL+/-0.55; P=.034) after contrast material injection compared with baseline (1.25 mg/dL+/-0.61). In group AT, creatinine significantly decreased 24 hours (1.21 mg/dL+/-0.74; P=.003) and 48 hours (1.17 mg/dL+/-0.69; P<.001) after contrast material injection compared with baseline (1.28 mg/dL+/-0.74). Group A had significantly higher maximal increases in creatinine than groups T and AT (P=.014). CONCLUSION: For prophylaxis of contrast-induced nephropathy in patients who are admitted to the intensive care unit and who receive 100 mL or more of contrast medium, theophylline is superior to acetylcysteine.  相似文献   
95.
96.
    
The medial septum and diagonal band complex (MS-DB) is believed to play a key role in generating theta oscillations in the hippocampus, a phenomenon critical for learning and memory. Although the importance of the MS-DB in hippocampal theta rhythm generation is generally accepted, it remains to be determined whether the MS-DB alone can generate hippocampal oscillations or is only a transducer of rhythmic activity from other brain areas. Secondly, it is known that hippocampal theta rhythm can be separated into an atropine-sensitive and insensitive component. However, it remains to be established if the MS-DB can generate both types of rhythm. To answer these questions, we used a new in vitro rat septohippocampal preparation placed in a hermetically separated two side recording chamber. We showed that carbachol activation of the MS-DB generated large theta oscillations in the CA1 and CA3 regions of the hippocampus. These oscillations were blocked by applying either the GABA(A) receptor antagonist bicuculline or the AMPA/kainate antagonist DNQX to the hippocampus. Interestingly, the application of the muscarinic receptor antagonist atropine produced only a partial decrease in the amplitude, without modification of the frequency, of theta. These results show for the first time, that upon optimal excitation, the MS-DB alone is able to generate hippocampal oscillations in the theta frequency band. Moreover, these MS-DB generated theta oscillations are mediated by muscarinic and nonmuscarinic receptors and have a pharmacological profile similar to theta rhythm observed in awake animals.  相似文献   
97.
    
Olfactory ensheathing cells (OECs) play a crucial role during neurogenesis of primary olfactory neurons. Transplantation of OECs is considered as a promising new therapy for central nervous system repair. Nevertheless, OECs are constituted of distinct subpopulations and their role during neurogenesis is not clearly understood. In particular, OECs from the olfactory bulb (OB) constitute a heterogeneous, but not yet isolated and characterized, population of cells. In our study, flow cytometry analyses of primary OB cultures, based on cell surface expression of low-affinity nerve growth factor receptor (p75), reveal the presence of two distinct populations of OECs. Indeed, some of them express a high level of p75 (P75High) and the other a low level of p75 (P75Low). Effects of OB microenvironment were assessed, and we were able to show that fibroblasts mediate the induction of these two populations through the secretion of soluble factors. To characterize P75High and P75Low OECs, cells were sorted based on their differential expression of p75. Microarray analyses revealed that P75High OECs overexpress genes implicated in modulation of extracellular matrix and cell sorting, whereas P75Low OECs overexpress genes involved in regulation of the inflammatory response and axonal guidance. These results permit, for the first time, to isolate the two distinct subpopulations of OECs from OB, and suggest their specific role during neurogenesis.  相似文献   
98.
    
We report three patients with a syndrome that fulfilled clinical and laboratory criteria for definite chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) who failed immunosuppressive treatment and eventually developed progressive amyotrophic lateral sclerosis (ALS). Mean disease duration was 23 months (13-38) before death. Two patients had a family history of ALS without mutations of the SOD1 gene. Postmortem examination in one patient showed an endoneurial infiltration of mononuclear cells in lumbar roots and distal and proximal peripheral nerves, mainly around myelinated fibers, with demyelination and axonal loss, consistent with CIDP. The spinal cord revealed severe neuronal loss in the anterior horn, axonal loss in the corticospinal tract, and large numbers of phagocytes in the anterior and lateral tracts, indicative of ALS. Whether demyelinating polyneuropathy was coincident with ALS or was a cause or consequence of motor neuron degeneration in these patients remains to be elucidated. This unusual combination may provide an important clue in elucidating the pathogenesis of ALS in some patients.  相似文献   
99.
  总被引:1,自引:0,他引:1  
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100.
  总被引:2,自引:0,他引:2  
We report a case of cerebral fat embolism which occurred in a 33-year-old man after a diaphyseal femoral fracture without cranial traumatism. The initial examination showed an incomplete picture of coma with tetrapyramidal syndrome and cutaneomucous purpura. There was no respiratory damage. We present a magnetic resonance spectroscopy analysis of the cerebral lesions observed in the initial phase of the embolism, as well as follow-up, which has strengthened the clinical and imaging features for the diagnosis.  相似文献   
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